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PY6040 > Inflammatory Bowel Disease > Flashcards

Inflammatory Bowel Disease Flashcards

1
Q

What is IBD

A

Inflammatory bowel disorder characterised by chronic and spontaneous relapsing of inflammation

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2
Q

Pathogenesis of IBD

A

Immune disease
Environmental factors (smoking, diet, hygiene, medical history)
Gut/microbial alterations
Genetic susceptibility

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3
Q

Microbiota

A

Group of microorganisms that reside in a previously established environment

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4
Q

Dysbiosis

A

An unhealthy change in the normal microbiota

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5
Q

Specialised epithelial cells

A

Goblet cells: Mucus, repair and inflammation modulatory factors
Paneth cells: Anti-microbial peptides

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6
Q

Mucosa innate immune function

A
  • Pattern recognition receptors (NOD-like receptors) that mediate responses to microbiota
  • Divert tolerance or inflammation pathways
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7
Q

Inflammatory processes

A
  • Breakdown in mucosal barrier function so Lamina propria exposed to antigens
  • Infiltration with immune cells (Neutrophils, macrophages, dendritic cells, natural killer cells, B and T cells)
  • Local elevation of TNF α, IL-1 β, IFN γ
  • Defective regulation of immunosuppression
  • Activated T cells activate other inflammatory cells like macrophages and B cells recruiting more inflammatory cells
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8
Q

T effector cells

A

Ulcerative colitis has excess Th2 and Th17 cells
Chron’s disease has excess Th1 and Th17 cells
They both have defect in Tregs

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9
Q

Genetic susceptibility

A
  1. Defects in mucosal barrier
    - Exposure to bacterial products
    - MUC19, OCTN, DLG5
  2. Defects in bacterial sampling
    - Pattern recognition receptors NOD2
    - Bacterial peptidoglycan receptor
    - LPS receptor
  3. Defects in immune response
    - IL23R defect
    - IL-10 pathway
    - INF γ gene
    - Autophagy genes (ATG16L1)
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10
Q

Laboratory tests

A 
Increased C-reactive protein
ESR increased
Platelet count increased
Hameoglobin decreased
Leukocytosis
-	Fecal calponectin
IBD antibodies are pANCA (Antineutrophil cytoplasmic antibody) and ASCA (Antisaccharomyces cerevisiae antibody)

Positive pANCA and negative ASCA = UC
Negative pANCA and positive ASCA = CD

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11
Q

Clinical signs of Chron’s Disease

A 
Abdominal pain
Perianal disease
Anorexia/Weight loss
Bloody diarrhoea
Growth failure

Occurs in any part of GIT and lesions discontinuous

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12
Q

Clinical signs of Ulcerative colitis

A

Bloody diarrhoea
Abdominal pain
Passage of mucus

Usually starts in rectum and spreads proximally in continuity

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13
Q

Macroscopic features

A

For Chron’s disease:

  • Transmural inflammation
  • Extends into the deeper layer of intestinal wall
  • Bowell wall thickened and rigid
  • Lumen narrowed

For Ulcerative colitis:
- Ulceration and inflammation of the inner lining of the colon and rectum

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14
Q

Th1, Th2 and Th17

A

Th1: IL-12, TNF α and IFN γ
Th2: IL-5, IL-13 and IFN γ, TNF α
Th17: IL-17 and IL-23

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15
Q

Chron’s and ulcerative colitis gene defects

A

Chron’s: MUC19, EP4 receptor (PTGER4), ATG16L1, PTPN2, card15, octn
Ulcerative colitis: IL-10 defects, INF γ, IL26 genes, PLA2G2E, CARD15, OCTN

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16
Q

Treatment options

A
  • Antibiotics
  • Anti-inflammatory
  • Immunosupressants
  • Biologicals
17
Q

Anti-inflammatory

A
  1. Aminosalicylates (5-ASA
    Activate PPARy
    Inhibit eicosanoid synthesis
    Inhibit production of proinflammatory cytokines
    Inhibit adhesion molecule expression
    Stimulate production of anti-inflammatory molecules
    Modulates proliferation, differentiation and survival of immune cells
    - Sulfasalazine, mesalazine, olsalazine, balsalazide
  2. Glucocorticoids
    Modify gene transcription
    Inhibit production of proinflammatory cytokines
    Inhibit synthesis of proinflammatory enzymes
    - Budesonide, Prednisone
18
Q

Immunosupressants

A
  1. Thiopurines i.e. Azathioprine, 6-mercaptopurin
    Inhibit T cell and B cell proliferation
  2. Methotrexate
    Inhibit production of proinflammatory mediators
  3. Cyclosporin
    Inhibit synthesis of IL-2 and IL-2R, inhibiting clonal expansion of T cells
19
Q

Anti-TNF agents

A

Adalimumab, infliximab and golimumab

  • Inhibits proinflammatory cytokine release i.e. IL-1, IL-6
  • Inactivates leukocyte
  • Induces inflammatory cells apoptosis
20
Q

Infliximab

A
  • Binds to TNF trimers preventing cytokine from binding to its receptor
  • Binds to membrane bound TNF α and neutralises its activity
  • Reduces serum TNF α levels
21
Q

Biologicals

A 
Anti TNF α: Infliximab, adalimumab, golimumab
Anti-IL23/IL12: Ustekinumab
Anti-α4: Natalizumab
Anti-α4β7: Vedolizumab
JAK inhibitor: Tofacitinib
Anti-IL6:Tocilizumab

PY6040 (23 decks)

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